GOALI: Catalytic Stereoselective Cross-Coupling Reactions

Boston College, Chestnut Hill MA

Investigators

Abstract

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor James Morken of Boston College and Dr. Robert Singer of Pfizer are studying the development of new chemical reactions that produce molecules having a well-defined three-dimensional topology. Because a significant fraction of molecules having a defined three-dimensional shape are present in newly approved drugs (44% of new pharmaceuticals in 2015), chemical reactions that can control this sp3-rich topology are valuable to the pharmaceutical and chemical industries. The goal of this research is to develop such reactions with the expectation that these processes will streamline drug-development and improve access to important medicines. This academic-industrial partnership is studying new palladium and copper-based reactions for their ability to act as effective catalysts to control the three dimensional topology of the product. They are also evaluating whether these catalysts can operate efficiently, economically, and with minimal production of hazardous waste. By being part of the collaboration through the GOALI (grant opportunities for academic liaison with industry) award, the undergraduate and graduate students involved in the research will acquire training that is critical to science-based careers in fields ranging from medicine to pharmaceuticals, and to chemistry. Under this GOALI award, the Morken research group at Boston College and collaborators led by Dr. Robert Singer at Pfizer are developing enantioselective cross-coupling reactions that operate on meso-diborylalkane substrates. Chiral catalysts are being developed that can affect cross-coupling reactions that selectively break the symmetry of the diboryl reactant and deliver products that retain one of the original boronic ester groups. In addition to the design of appropriate reactions and the examination of their synthetic utility, the team is developing concise routes to new chiral phosphine ligands that are expected to not only be useful in the the diborylalkane reactions but also in other catalytic transformations. Additionally, mechanistic experiments are being carried out to determine why diboryl substrates are unusually reactive in cross-coupling reactions and whether the gained information can be used in the design of new reactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.